(R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3-fluorophenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | 672965-17-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3-fluorophenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS: 672965-17-2
• 化学式: C₂₄H₃₀FN₃O₃S
• 分子量: 459.585
• InChiKey: ZJVFAISXRDNYOS-PCCBWWKXSA-N

物化性质

• 沸点：
  734.4±60.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.36
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  95.66
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3-fluorophenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 sodium hydroxide 、 三乙胺 、 氯磷酸二苯酯 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 生成 (R)-3-[(2S,3S)-4-(3-Fluoro-phenyl)-2-hydroxy-3-(3-hydroxy-2-methyl-benzoylamino)-butyryl]-5,5-dimethyl-thiazolidine-4-carboxylic acid 2-methyl-benzylamide
  参考文献：
  名称：

  Structure–activity and structure–metabolism relationships of HIV protease inhibitors containing the 3-hydroxy-2-methylbenzoyl-allophenylnorstatine structure

  摘要：

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenyinorstatine [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were designed and synthesized. From the structure-metabolism relationship of this type of HIV protease inhibitors, the compounds having para substitution of the phenyl ring of Apris and/or 2,6-disubstitution of the P2' benzylamine were found to be able to avoid the P2 phenol glucuronidation that occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main metabolic pathways of SM-319777. These new analogues, such as SM-322377, had more desirable pharmacokinetic profiles and more potent antiviral activity against not only wild type HIV-1 but also the multi-drug-resistant HIV-1 than SM-319777. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.037
• 作为产物：
  描述：

  2-甲基苯甲基胺 在 盐酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 氯磷酸二苯酯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3-fluorophenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Structure–activity and structure–metabolism relationships of HIV protease inhibitors containing the 3-hydroxy-2-methylbenzoyl-allophenylnorstatine structure

  摘要：

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenyinorstatine [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were designed and synthesized. From the structure-metabolism relationship of this type of HIV protease inhibitors, the compounds having para substitution of the phenyl ring of Apris and/or 2,6-disubstitution of the P2' benzylamine were found to be able to avoid the P2 phenol glucuronidation that occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main metabolic pathways of SM-319777. These new analogues, such as SM-322377, had more desirable pharmacokinetic profiles and more potent antiviral activity against not only wild type HIV-1 but also the multi-drug-resistant HIV-1 than SM-319777. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.037